Genetic abnormalities associated with hematological malignancies alter the normal structure and function of genes that control cell growth, differentiation or death either in a positive or negative manner (1). The genes involved can be grouped into two general categories. The first group involves the structural alternation of a normal cellular gene, named proto-oncogen, whose protein product induce uncontrolled proliferation or loss of contact inhibition. The second group consists of genes, whose loss of function is associated with malignant transformation, and are referred to as tumor suppressor genes (2). There are several tumor suppressor genes known to be important in evolution of acute leukemia. Both p15 and p16 have been found to be homozygously deleted in 6% to 28% of B lineage acute lymphoblastic leukemia (ALL) patients, while p16 was found to be deleted in 41% to 83% in T cell ALL (3). Others showed that p16 can be functionally inactivated by either point mutations or hypermethylation of the p16 promoter region (4). Another tumor suppressor gene, retinoblastoma gene, was reported to be inactivated at a low frequency in T cell ALL patients (5). P53 another important tumor suppressor gene, was found to be functionally inactivated in 50% of samples from patients at relapse, suggesting that p53 mutations may be important in disease progression (6). Others hypothesized that loss of a putative tumor suppressor named TEL may promote leukemogenesis by affecting cell growth and/or by altering cell adhesion (7).
Recently, a novel human apoptosis inducing protein (ARTS), which induces cell killing by proapoptotic inducers such as TNF β, Fas, etoposide, arabinoside (ara-c) and TNF α, was identified. ARTS is a member of the septin family of proteins and is encoded by 823 base pair cDNA sequence, encoding a predicted polypeptide of 274 amino acids. ARTS contains a P-loop GTP-binding domain, conserved in different classes of ATP/GTPases, including CED-4 and Apaf-1, which are major regulators of apoptosis.